- MeSH
- cauda equina * diagnostické zobrazování patologie MeSH
- diferenciální diagnóza MeSH
- fatální výsledek MeSH
- lidé MeSH
- lymfomatózní neuropatie * diagnostické zobrazování patologie MeSH
- progrese nemoci MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- kazuistiky MeSH
OBJECTIVE: In this experimental study, we aimed to determine whether platelet-rich plasma (PRP) is a suitable preservative for dermo-epidermal grafts. An additional objective was to investigate how long grafts can be stored without biological degradation. METHODS: We compared pig skin graft preservation using PRP versus saline solution and crystalloid Custodiol®, which is used for hypothermic preservation of organs for transplantation. Grafts (10 × 10 mm) were placed on gauze impregnated with one of the tested solutions, and stored for 3, 7, 11, and 15 days at a constant temperature of 4°C. We evaluated a total of 240 pig skin samples: 120 by histopathology and 120 by fluorescence optical microscopy. RESULTS: Overall, Custodiol® solution appeared to be the best medium for preservation of dermo-epidermal grafts, with beneficial properties manifested on days 7 and 11. Although we expected PRP to be a better preservative than saline, this was not confirmed by our results, as we found no significant difference between these two media. In fact, by day 3, the histopathological results were better with standard saline solution than with PRP. On day 15, with each tested solution, some samples showed histological changes that are incompatible with graft viability. CONCLUSION: Overall, Custodiol® appears to be the best medium for dermo-epidermal graft preservation. Moreover, the present findings suggest a maximum graft storage time of 11 days in all of the tested solutions. We do not recommend using grafts stored for 15 days, due to isolated signs of graft biodegradation with all solutions.
- Publikační typ
- časopisecké články MeSH
The criteria for distinction between independent primary tumors and metastasis from one site to the other in synchronous endometrioid endometrial and ovarian carcinoma (SEO) has been a matter of dispute for a long time. In our study we performed a comprehensive clinico-pathological and molecular analysis of 22 cases of SEO. Based on conventional clinico-pathological criteria the cases were classified as independent primary tumors (10 cases) and metastasis from one location to the other (12 cases). All tumors were analyzed by NGS with a panel of 73 genes (219 kbp). Clonal origin was confirmed in all cases by at least one shared mutation in PTEN, AKT1, PIK3CA, KRAS, TP53 and ARID1A. Two patients carried germline pathogenic mutation in cancer-predisposing genes BRCA1 or BARD1. Microsatellite instable phenotype was detected in 5/22 (22.7%) SEO, but in one case only in the endometrial tumor. In conclusion, our results showed that all 22 SEOs were clonally related, irrespectively of their clinico-pathological features. Even low grade and low stage tumors classified as independent primaries, according to the conventional morphological criteria, have a clonal origin. From the practical point of view, only the conventional morphological criteria should be used for the classification (staging) of these tumors. However, molecular profiling of these tumors may have prognostic and predictive meaning.
- Publikační typ
- časopisecké články MeSH
Východiska: Použití nivolumabu v léčbě metastatického melanomu se v uplynulých letech stalo terapeutickým standardem. I přes jeho nepopiratelnou účinnost se však mohou objevit nežádoucí reakce, vč. akutního poškození jater. Hepatotoxicita způsobená nivolumabem je obvykle popisována jako zvýšení hladin jaterních enzymů s příznaky či bez příznaků. Informace o histopatologických projevech této toxicity existují v omezené míře. Případ: Uvádíme případ 38leté ženy s metastazujícím maligním melanomem, u které došlo k poškození jater po jedné dávce nivolumabu. Jelikož žádné vyšetření v podobě biochemie, virologie, autoprotilátek ani zobrazovacích metod neodhalilo příčinu jaterního selhávání, byla provedena jaterní biopsie. Histopatologické vyšetření prokázalo edém v portálních polích a smíšený zánět sestávající z eozinofilních a neutrofilních granulocytů. Hlavním nálezem byla prominentní, převážně intracelulární cholestáza. Závěr: Podle našich znalostí nebyl tento typ jaterního postižení v souvislosti s léčbou nivolumabem dosud popsán. Tento typ jaterního poškození může být spojován s vyšší rezistencí na léčbu kortikosteroidy, s nutností agresivnějšího přístupu či s použitím dalších imunosupresiv, jako např. mykofenolátu mofetil. Tento případ dále upozorňuje na potřebnou obezřetnost, ale i nutnost dobré informovanosti o možných nežádoucích účincích souvisejících s imunoterapií, které, ač nemusejí být časté, mohou být potenciálně život ohrožující.
Background: The use of nivolumab in the treatment of metastatic melanoma has become well established during past years. Despite its undeniable efficacy, immune-related side effects may occur, including acute liver injury. Liver toxicity caused by nivolumab is usually observed as liver enzyme elevation with mild or no symptoms; further, there is limited information regarding any histopathological findings. Case: We report a case of a 38-year-old woman with metastatic melanoma who developed unusual nivolumab-induced hepatic injury after a single dose of nivolumab. A liver biopsy was performed to assess the aetiology of hepatic lesions as no other analysis concerning biochemistry, virology, autoantibodies, nor imaging studies revealed any pathology. The histopathological analysis showed an oedema in the portal fields and mixed inflammation consisting of eosinophilic and neutrophilic granulocytes. The major finding was a prominent, predominantly intracellular, cholestasis. Conclusion: To our knowledge, no such histopathological pattern of liver injury has been described in relation to nivolumab therapy elsewhere. This type of liver injury shows higher resistance to corticosteroids, which may warrant upfront high-dose corticotherapy combined with other immunosuppressive agents, including mycophenolate mofetil. This case highlights a necessary awareness regarding immunotherapy-related adverse events, which could be severe and potentially life-threatening.
- MeSH
- autoimunita MeSH
- dospělí MeSH
- hepatitida etiologie MeSH
- lékové postižení jater * diagnóza etiologie MeSH
- lidé MeSH
- melanom farmakoterapie MeSH
- metastázy nádorů farmakoterapie MeSH
- nivolumab * škodlivé účinky toxicita MeSH
- protinádorové látky škodlivé účinky toxicita MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
BACKGROUND: Great progress has recently been made in the treatment of metastatic renal cell carcinoma, including the introduction of nivolumab, an immune checkpoint inhibitor. Despite promising results, this treatment brings a completely new spectrum of adverse events, distinct from those experienced with small-molecule kinase inhibitors. Neurologic immune-related adverse events may be serious and potentially life-threatening complications requiring immediate immunosuppressive therapy. Only a few cases of immune-related encephalitis induced by checkpoint inhibitors have been described and the data regarding the management of this serious adverse event are limited. CASE PRESENTATION: We report the case of a 63-year-old white man with metastatic renal cancer who developed severe chorea-like dyskinesia during nivolumab therapy. The findings on brain magnetic resonance imaging and flow cytometry of cerebrospinal fluid, and the positivity of anti-paraneoplastic antigen Ma2 immunoglobuline G class autoantibodies were consistent with a diagnosis of immune-related encephalitis. High-dose intravenous corticosteroid therapy was started immediately, with no signs of improvement, even when infliximab was added. Our patient refused further hospitalization and was discharged. Three weeks later, he presented with signs of severe urosepsis. Despite intensive treatment, he died 4 days after admission. CONCLUSIONS: The management of less frequent immune-related adverse events has not been fully established and more information is required to provide uniform recommendations. Immune-related encephalitis is a severe and potentially fatal complication requiring immediate hospital admission and extensive immunosuppressive therapy. The examination of cerebrospinal fluid for paraneoplastic antibodies, such as anti-N-methyl-D-aspartate receptor and anti-Ma2 antibodies, in order to distinguish autoimmune etiology from other possible causes is essential and highly recommended.
- MeSH
- encefalitida chemicky indukované MeSH
- karcinom z renálních buněk farmakoterapie sekundární MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin farmakoterapie patologie MeSH
- nivolumab škodlivé účinky MeSH
- protinádorové látky imunologicky aktivní škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Klíčová slova
- RASSF1, NUT midline carcinoma,
- MeSH
- imunohistochemie MeSH
- jaderné proteiny MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA MeSH
- mikro RNA MeSH
- nádory nosu * genetika klasifikace patologie terapie MeSH
- nádory vedlejších dutin nosních * genetika klasifikace patologie terapie MeSH
- onkogenní proteiny MeSH
- regulace genové exprese MeSH
- senioři MeSH
- translokace genetická MeSH
- výzkum MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
